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      Pathophysiological Mechanisms of Chronic Venous Disease and Implications for Venoactive Drug Therapy

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          Abstract

          Chronic venous disease (CVD) is a common pathology, with significant physical and psychological impacts for patients and high economic costs for national healthcare systems. Throughout the last decades, several risk factors for this condition have been identified, but only recently, have the roles of inflammation and endothelial dysfunction been properly assessed. Although still incompletely understood, current knowledge of the pathophysiological mechanisms of CVD reveals several potential targets and strategies for therapeutic intervention, some of which are addressable by currently available venoactive drugs. The roles of these drugs in the clinical improvement of venous tone and contractility, reduction of edema and inflammation, as well as in improved microcirculation and venous ulcer healing have been studied extensively, with favorable results reported in the literature. Here, we aim to review these pathophysiological mechanisms and their implications regarding currently available venoactive drug therapies.

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          Most cited references126

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          The care of patients with varicose veins and associated chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

          The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE 1) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C(2); GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration ≥500 ms, vein diameter ≥3.5 mm) located underneath healed or active ulcers (CEAP class C(5)-C(6); GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B). Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
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            The epidemiology of chronic venous insufficiency and varicose veins.

            Chronic venous disease is a common condition presenting to physicians in Western Europe and the United States. This article provides a comprehensive review of the published literature in the English language, from 1942 to the present, and focuses on the prevalence of chronic venous insufficiency and varicose veins, as well as the involved risk factors. Prevalence estimates vary widely by geographic location, with the highest reported rates in Western countries. Reports of prevalence of chronic venous insufficiency vary from < 1% to 40% in females and from < 1% to 17% in males. Prevalence estimates for varicose veins are higher, <1% to 73% in females and 2% to 56% in males. The reported ranges in prevalence estimations presumably reflect differences in the population distribution of risk factors, accuracy in application of diagnostic criteria, and the quality and availability of medical diagnostic and treatment resources. Established risk factors include older age, female gender, pregnancy, family history of venous disease, obesity, and occupations associated with orthostasis. Yet, there are several factors that are not well documented, such as diet, physical activity and exogenous hormone use, which may be important in the development of chronic venous disease and its clinical manifestations.
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              Chronic venous insufficiency.

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                05 June 2018
                June 2018
                : 19
                : 6
                : 1669
                Affiliations
                [1 ]Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; joel.sousa@ 123456jmellosaude.pt
                [2 ]Departamento de Angiologia e Cirurgia Vascular, Hospital CUF Porto, 4100-180 Porto, Portugal
                Author notes
                Author information
                https://orcid.org/0000-0002-7881-7702
                Article
                ijms-19-01669
                10.3390/ijms19061669
                6032391
                29874834
                7e8d5283-f76b-4618-aa04-aa1be0e9b46e
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 March 2018
                : 29 May 2018
                Categories
                Review

                Molecular biology
                chronic venous disease,chronic venous insufficiency,pathophysiology,inflammation,endothelial dysfunction,venoactive drugs,flavonoid,micronized purified flavonoid fraction,mpff

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